Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

A new massively-parallel transposon mutagenesis approach comparing multiple datasets identifies novel mechanisms of action and resistance to triclosan

Muhammad Yasir, A. Keith Turner, View ORCID ProfileSarah Bastkowski, Andrew J. Page, Andrea Telatin, Minh-Duy Phan, Leigh G. Monahan, Aaron E. Darling, Mark A. Webber, Ian G. Charles
doi: https://doi.org/10.1101/596833
Muhammad Yasir
Quadram Institute Bioscience, Norwich Research Park, Norwich, NR4 7UQ, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
A. Keith Turner
Quadram Institute Bioscience, Norwich Research Park, Norwich, NR4 7UQ, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Sarah Bastkowski
Quadram Institute Bioscience, Norwich Research Park, Norwich, NR4 7UQ, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Sarah Bastkowski
Andrew J. Page
Quadram Institute Bioscience, Norwich Research Park, Norwich, NR4 7UQ, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Andrea Telatin
Quadram Institute Bioscience, Norwich Research Park, Norwich, NR4 7UQ, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Minh-Duy Phan
School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia 4072, Queensland, Australia
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Leigh G. Monahan
The ithree institute, University of Technology Sydney, PO Box 123, Broadway NSW 2007, Australia
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Aaron E. Darling
The ithree institute, University of Technology Sydney, PO Box 123, Broadway NSW 2007, Australia
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Mark A. Webber
Quadram Institute Bioscience, Norwich Research Park, Norwich, NR4 7UQ, UKUniversity of East Anglia, Norwich Research Park, Norwich, NR4 7TJ
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: mark.webber@quadram.ac.uk
Ian G. Charles
Quadram Institute Bioscience, Norwich Research Park, Norwich, NR4 7UQ, UKUniversity of East Anglia, Norwich Research Park, Norwich, NR4 7TJ
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Preview PDF
Loading

Abstract

The mechanisms by which antimicrobials exert inhibitory effects against bacterial cells and by which bacteria display resistance vary under different conditions. Our understanding of the full complement of genes which can influence sensitivity to many antimicrobials is limited and often informed by experiments completed in a small set of exposure conditions. Capturing a broader suite of genes which contribute to survival under antimicrobial stress will improve our understanding of how antimicrobials work and how resistance can evolve. Here, we apply a new version of ‘TraDIS’ (Transposon Directed Insert Sequencing); a massively parallel transposon mutagenesis approach to identify different responses to the common biocide triclosan across a 125-fold range of concentrations. We have developed a new bioinformatic tool ‘AlbaTraDIS’ allowing both predictions of the impacts of individual transposon inserts on gene function to be made and comparisons across multiple TraDIS data sets. This new TraDIS approach allows essential genes as well as non-essential genes to be assayed for their contribution to bacterial survival and growth by modulating their expression. Our results demonstrate that different sets of genes are involved in survival following exposure to triclosan under a wide range of concentrations spanning bacteriostatic to bactericidal. The identified genes include those previously reported to have a role in triclosan resistance as well as a new set of genes not previously implicated in triclosan sensitivity. Amongst these novel genes are those involved in barrier function, small molecule uptake and integrity of transcription and translation. These data provide new insights into potential routes of triclosan entry and bactericidal mechanisms of action. Our data also helps to put recent work which has demonstrated the ubiquitous nature of triclosan in people and the built environment into context in terms of how different triclosan exposures may influence evolution of bacteria. We anticipate the approach we show here that allows comparisons across multiple experimental conditions of TraDIS data will be a starting point for future work examining how different drug conditions impact bacterial survival mechanisms.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
Back to top
PreviousNext
Posted April 04, 2019.
Download PDF
Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
A new massively-parallel transposon mutagenesis approach comparing multiple datasets identifies novel mechanisms of action and resistance to triclosan
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
Share
A new massively-parallel transposon mutagenesis approach comparing multiple datasets identifies novel mechanisms of action and resistance to triclosan
Muhammad Yasir, A. Keith Turner, Sarah Bastkowski, Andrew J. Page, Andrea Telatin, Minh-Duy Phan, Leigh G. Monahan, Aaron E. Darling, Mark A. Webber, Ian G. Charles
bioRxiv 596833; doi: https://doi.org/10.1101/596833
Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
Citation Tools
A new massively-parallel transposon mutagenesis approach comparing multiple datasets identifies novel mechanisms of action and resistance to triclosan
Muhammad Yasir, A. Keith Turner, Sarah Bastkowski, Andrew J. Page, Andrea Telatin, Minh-Duy Phan, Leigh G. Monahan, Aaron E. Darling, Mark A. Webber, Ian G. Charles
bioRxiv 596833; doi: https://doi.org/10.1101/596833

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Microbiology
Subject Areas
All Articles
  • Animal Behavior and Cognition (1524)
  • Biochemistry (2479)
  • Bioengineering (1731)
  • Bioinformatics (9670)
  • Biophysics (3896)
  • Cancer Biology (2968)
  • Cell Biology (4189)
  • Clinical Trials (135)
  • Developmental Biology (2624)
  • Ecology (4098)
  • Epidemiology (2031)
  • Evolutionary Biology (6894)
  • Genetics (5204)
  • Genomics (6496)
  • Immunology (2183)
  • Microbiology (6937)
  • Molecular Biology (2751)
  • Neuroscience (17261)
  • Paleontology (126)
  • Pathology (425)
  • Pharmacology and Toxicology (705)
  • Physiology (1056)
  • Plant Biology (2488)
  • Scientific Communication and Education (643)
  • Synthetic Biology (831)
  • Systems Biology (2687)
  • Zoology (429)